tbuckley/cabot-search huggingface dataset:
PB2236: POPULATION BASED INCIDENCE OF ESSENTIAL THROMBOCYTHEMIA: AN ALBANIAN STUDY (2007-2021)
Authors: Adela Perolla, Elsuarta Çalliku, Alma Cili, Tatjana Caja, Polikron Pulluqi, Arben Ivanaj
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Essential thrombocythemia (ET) first recognized in 1934 and used to be called at the time also hemorrhagic thrombocytosis or primary thrombocytosis, is a rare blood disease. With an incidence from 0.2 to 2.5 cases/ 100 000 people per year it was classified as myeloproliferative neoplasms (MPN) in 1951 by Damesheck. Myeloproliferative neoplasms include Essential Thrombocythemia, Primary Myelofibrosis and Polycythemia Vera. ET according to the World Health Organization is a disease characterized by thrombocytosis more than 450000/ mm3 in the peripheral blood, showing megakaryocytic hyperplasia in the bone marrow and with about 55% of cases presenting positivity for JAK 2 mutation. We present here our unique data on the incidence of Essential Thrombocythemia in Albania. Aims: The aim of our study is to evaluate the incidence, age, and sex distribution of Essential Thrombocythemia patients in the Albanian population during the period from 2007-2021. Methods: We have included in our study and analyzed the data of all patients, more than 18 years old diagnosed with ET in our Service of Hematology, Mother Tereza Hospital from 2007 to 2021.The data were collected from the registries in our Service of Hematology and from the registries in the Department of Statistics, UHC “Mother Teresa” for the period from 2007 to 2021 and were analyzed with SPSS 25.0. Results: In our Service of Hematology, during the interval of time from the year 2006 to the year 2021, were diagnosed 64 [100%] patients with ET, 28 pts (43,8%) males, and 36 pts (56,3%) female. The median age at the moment of the diagnosis resulted in 56,2 years old (interval range 22-80 years old). The crude median age adjusted incidence of ET is about 5,8 new cases per year in the adult population Albanian population of 2 163 802 inhabitants, and the annual age adjusted incidence of ET patients resulted in 2,9 new cases per 100 000 inhabitants, with an increase13 new cases in 2016 and a peak in 2018 (15 new cases). The age adjusted annual incidence of ET according to sex distribution resulted respectively in 3,2 new cases per 100 000 females and 2,6 new cases per 100 000 males. Summary/Conclusion: Essential Thrombocythemia is a rare indolent Myeloproliferative Neoplasm with a good prognosis and a life expectancy more than 30 years in patients younger than 60 years old, despite this, 20% of the patients develops thrombotic events which can be life-threatening. Further study is needed to access the disease burden in our country and to estimate the population eligible to receive the novel – era medications. Keywords: Essential Thrombocytemia
PB1727: EVALUATION OF POST-TREATMENT SECONDARY CANCERS IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH MODIFIED ST. JUDE TOTAL XIII AND TOTAL XV PROTOCOLS.
Authors: Hilal Eda Korkmaz Ünlü, Bariş Kuşkonmaz, Şule Ünal Cangül, Melis Gültekin Bahadir, Şevkiye Selin Aytaç Eyüpoğlu, Fatma Gümrük
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood period and some complications such as secondary cancers, infertility, and neurocognitive disorders may develop in the long term due to ALL treatment. Aims: In this study, it was aimed to analyze secondary cancers of ALL patients. Methods: Pediatric patients aged 1-18 years who were diagnosed with ALL between January 1, 1997 and January 30, 2016 at Hacettepe University Department of Pediatric Hematology were retrospectively analyzed. Results: In this study, 245 and 183 patients who were treated with Modified St. Jude Total XIII and Total XV protocols respectively, were included and the median follow-up time was 15.5 years. A total of 10 (4.5%) cases with secondary cancer were observed who were treated with Modified St. Jude Total XIII protocol, compared with no cases who were treated with Modified St. Jude Total XV protocol (p=0.006). Secondary cancers were glial tumors (n=2), meningioma (n=1), thyroid cancer (n=2), acute myeloblastic leukemia (n=2), squamous cell carcinoma of the tongue (n=1), breast cancer (n=1), and T-cell lymphoblastic lymphoma (n=1). The median time to develop secondary central nervous system tumors from the time of the diagnosis was 14 (8.4-23.3) years, while the median time to develop secondary acute myeloid leukemia was 3 (2.2-3.8) years. When compared patients who developed secondary cancers with the patients who did not, there was no statistical difference in terms of gender, age at diagnosis, initial white blood cell count, immune phenotype, risk groups, relapse site, radiation therapy, and radiation therapy site (p>0.05). However, multivariate analysis revealed that traumatic LP increases the risk of developing secondary cancer 4.8 times and relapse 4.5 times. respectively) The five-year overall survival rate of patients who were treated with Modified St. Jude Total XIII protocol was 85.8± 2.4% and event-free survival was 78.7±2.8%. Five-year overall survival was 89.2±2.3% and event-free survival was 85.6±2.6% in patients who were treated with Modified St. Jude Total XV protocol. When comparing patients with and without secondary cancer, there is no statistically significant difference between the five-year and ten-year overall survival rates. Summary/Conclusion Considering long-term outcomes in a large group of leukemias, we analyzed the many diagnostic and therapeutic features that may affect secondary cancer in this study. In conclusion; reducing the problems that ALL patients may encounter in the long term should be one of the goals of ALL treatment and expanding knowledge to be obtained in that will contribute to this. Keywords: Acute lymphoblastic leukemia, Second malignancy
PB1764: SEGMENTATION AND CLASSIFICATION OF BONE MARROW CELLS FROM MULTI-PRECISION NUMERIZATION OF BONE MARROW SMEARS (BMS) FROM PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) USING AI TECHNIQUES
Authors: Achraf Bennis, Philippe Leleux, Alban Canali, Caroline De Pourtales, Sandrine Mouysset, David Simoncini, Pierre Brousset, Francois-Xavier Frenois, Christian Recher, Jean-Marc Alliot, Jean-Baptiste Rieu, Sarah Bertoli
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: The assessment of bone marrow (BM) cells is a central component for the diagnosis of AML. However, the manual assessment of BMS and counting of differentiated cells is a time-consuming method that depends on the experience and abilities of cytomorphologists and is not fully reproducible. Aims: In this study, we develop a pipeline for the automatic segmentation and classification of cells from BMS of patients with AML using Machine Learning (ML) and Computer Vision techniques. Methods: Whole BMS slides from 647 patients diagnosed with AML between 1/2017 and 12/2020 in Toulouse University Hospital were numerized using Panoramic 250 Flash II (3DHISTECH) scanner to obtain high-definition pictures in a.MRXS format, providing multiple magnification levels whose highest corresponds to 823 X (121nm/pixel). To analyze BMS images, we designed a pipeline separated into 3 steps as described below: first, we pre-selected tiles at the deepest zoom level most likely to contain exploitable cells to define areas of interest (AOI). For this purpose, we proposed a two-tier approach to filter fixed-size tiles on two zoom levels consecutively, using a combination of a pixel-wise k-means method and decision trees using textural features. Second, we extracted BM cells from the AOI. In this step, we considered two approaches: segmentation with an in-house segmentation software, which implements a genetic algorithm to find the cells, and a deep-learning-based model called Faster-RCNN, used for cell detection in the state-of-the-art. The former method only requires a low number of annotated images to train, but the training of the second one is much faster. In the third and final step, we combined the computation of radiomics features with ML methods to classify the extracted single cell images in a semi-supervised and unsupervised manner. Results: We were able to design a pipeline allowing automatic BM cell segmentation and classification, to identify between 1k and 1.5k cells from each BMS. At a lower magnification, we were also able to design a pipeline to identify megakaryocytes. We will show the entire multi-step pipeline and examples of automatically extracted and classified cells. Summary/Conclusion: Running our AI-based pipeline shows encouraging results in terms of extraction and classification of cells from BMS of AML. Our work will lead to the development of an AI tool to support cytomorphologists in the assessment of BMS from patients with AML. It will also permit the constitution of an AML bone marrow cells library Keywords: AML, Acute myeloid leukemia, Artificial intelligence
PB1805: BREAKING A PARADIGM: LOSS OF STAT3 INCREASES INVASION IN MLL-AF9-DRIVEN ACUTE MYELOID LEUKEMIA
Authors: Bernhard Zdársky, Sophie Edtmayer, Stefanie Boigenzahn, Agnieszka Witalisz-Siepracka, Kerstin Fiedler, Stefanie Weiss, Dagmar Stoiber-Sakaguchi
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Deregulated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is implicated in the pathogenesis of acute myeloid leukemia (AML), a heterogenous disease with poor prognosis. In 44% of AML patients, STAT3 displays constitutive activity which is associated with short disease-free survival. Various strategies for selective targeting of JAK-STAT signaling have demonstrated promising results in vitro and in vivo with some compounds reaching clinical trials for AML. However, several drug candidates have failed to provide therapeutic benefit, which is probably due to the heterogenicity behind AML development and progression. Aims: The goal of the present study is to investigate the detailed molecular mechanisms of STAT3 in AML development. Furthermore, we want to evaluate its role in the progression of different AML subtypes and to identify STAT3-targets that could be potential therapeutic molecules. Methods: Using CRISPR/Cas9 we generated STAT3-deficient human AML cell lines. The cell lines were characterized via flow cytometry, Western blot and qPCR and used for transplantation via tail vein into immunocompromised NSG mice. Results: AML cells lacking STAT3 showed no major impairment in survival and proliferation under basal conditions in vitro. STAT3 knockout (KO) AML (M6) HEL cells were less resistant to different drug treatments, whereas AML (M5) THP-1 STAT3 KO cells were generally more resistant. Interestingly, loss of STAT3 in THP-1 cells increased ZEB-1 and CXCR4 expression, two essential regulators of epithelial mesenchymal transition (EMT), cell migration and invasion. Animals transplanted with STAT3-deficient THP-1 cells showed accelerated disease progression, poorer overall survival, and increased liver infiltration, whereas there was no difference between the control group and mice injected with STAT3 KO HEL cells. Summary/Conclusion: We uncovered a paradigm shift in understanding the key function of STAT3 in metastatic progression in AML, which might be an explanation for the diverse treatment outcomes in patients. Our data indicate a surprising novel role of STAT3 in regulating invasive infiltration in MLL-AF9-driven AML. As a next step, we aim to identify AML subgroups that would benefit from therapeutical inhibition of STAT3 targets, in which STAT3 and e.g., ZEB-1 and CXCR4 act as prognostic marker for risk stratification, avoiding both over- and undertreatment of AML patients. Keywords: Acute myeloid leukemia, Metastasis, STAT3, Liver
PB2082: BONE MORPHOGENIC PROTEIN-6 PROMOTES THE PROLIFERATION AND INHIBITS APOPTOSIS IN MULTIPLE MYELOMA
Authors: Jiaqi Fu, Xing Cui
Journal: HemaSphere (2023)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Previous studies have shown that BMP6 could significantly inhibit the proliferation of myeloma cell lines and in vitro angiogenesis and is considered a protective factor for multiple myeloma (MM)1. Nevertheless, BMP6 also has tumor-promoting effects in studies of different other malignancies, which may be due to the lack of interactions with other cells within bone marrow microenvironment in myeloma cell experiments2,3. Moreover, emerging knowledge supports that BMP6 could directly promote neovessel formation, thus possibly serving as a target in pro/anti-angiogenic therapy4,5. Therefore, the role of BMP6 in MM progression needs further exploration. Aims: To further investigate the role of BMP6 in MM progression. Methods: RNA-Seq analysis of CD138-positive cells isolated from BM aspirates of MM patients (n = 3) and PBMCs of healthy donors (n = 4) was performed to generate the mRNA profiling database. Then, qRT‒PCR was used to verify the expression of BMP6. Twenty MM patients were assessed to evaluate the prognostic value of BMP6 and we next assessed the expression of BMP6 in both high-risk and low-risk patients by RNA-FISH. In vitro experiments were performed to determine the influence of BMP6 on the viability and apoptosis of U266 cells. Results: 5905 differently expressed genes were identified (Figure A, B). BMP6 was significantly upregulated in MM and was validated by qRT‒PCR (Figure C). Diagnostic accuracy of BMP6 was calculated via Receiver operating characteristic (ROC) curve (area under curve (AUC)=0.894, 95% CI 0.744 to 1.000) (Figure D). Kaplan‐Meier analysis revealed that higher BMP6 expression predicted shorter overall survival (OS) (Figure E). RNA-FISH showed that BMP6 was more highly expressed in CD138-positive cells of high-risk group patients than in low-risk group (Figure F). The CCK-8 and flow cytometry assay exhibited that the knockdown of BMP6 significantly decreased cell viability and promoted the apoptosis of U266 cells (Figure G, H).Summary/Conclusion: This is the first study focused on examining the BMP6 expression pattern in MM patients. Its initial findings indicate potential prognostic significance of BMP6 expression and demonstrated that BMP6 could promote the proliferation and inhibit the apoptosis of myeloma cells. Keywords: Multiple myeloma
PB2283: IN THE ERA OF IMMUNOPHENOTYPING AND MOLECULAR DIAGNOSTICS DOES MORPHOLOGY PLAY AN ESSENTIAL ROLE IN DIFFERENTIATING HAIRY CELL LEUKEMIA FROM ITS MIMICS?
Authors: Priyavadhana Balasubramanian, Harish Chandra, Samikshya Thapa, Anupa Khanal, Neha Singh, Arvind Kumar Gupta, Uttam Nath
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Hairy cell leukemia (HCL) accounts for 2% of all lymphoid leukemias. It is characterized by splenomegaly, cytopenias and atypical lymphoid cells with circumferential cytoplasmic projections. While HCL responds well to chemotherapy, the other morphological differential diagnosis such as hairy cell leukemia variant (HCL-v) and splenic marginal zone lymphoma (SMZL) do not respond well to HCL therapy, and have a significantly lower survival. Distinguishing HCL from HCLv and SMZL can be challenging as clinical and pathologic findings often overlap. Aims: To analyse the clinical, morphological and immunophenotypic features of HCL, HCL-v and SMZL and to evaluate the role of morphological features in differentiating these entities. Methods: This was an observational study which included eight cases of HCL and its mimics diagnosed over a 4 and a half year period. The clinical details, and complete blood counts were recorded. The peripheral smear (PS) and bone marrow aspirate (BMA) slides were reviewed for morphological features such as cytoplasmic projections, amount of cytoplasm, nuclear shape and nucleoli. Bone marrow biopsy (BMB) slides were reviewed for cellularity, pattern and percentage of marrow infiltration, and residual hematopoiesis. Flow cytometry was done in 3 cases which confirmed the diagnosis. Immunohistochemistry (IHC) panel of CD20, CD3, CD5, CD10, Cyclin D1, CD11c, CD25, CD103, CD123 and Annexin A 1 was done in other cases. Results: There were 5 cases of HCL, 2 cases of HCLv and 1 case of SMZL. All cases of HCL and SMZL had pancytopenia while HCLv had normal or increased total counts. Cytoplasmic projections were seen in 60% of HCL, and 100% of HClv. Prominent nucleoli were seen in HCLv (100%) but not in HCL. HCL showed significantly greater marrow infiltration over HCL-v. Marrow was hypocellular in 80% of HCL. On immunophenotyping (IPT), HCL expressed CD19, CD11c, CD25, CD103 and CD123 whereas HCLv lacked CD25. Annexin was positive in all cases of HCL while negative in HCLv and SLVL. (Table 1). Summary/Conclusion: This case series highlights the importance of identifying the subtle morphological features on peripheral smear, BMA/BMB that help in diagnosing HCL and its mimics. The ability to narrow down the IHC panel based on morphology will be helpful in limited resource settings. Table 1: Morphological findings in peripheral blood and bone marrow in HCL, HCLv and SMZL.Keywords: Hairy cell leukemia, Immunophenotype, Splenic marginal zone lymphoma
PB2409: CLINICAL PROGNOSTIC MODEL OF LIVER FAILURE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Qingyuan Qu, Menglin LI, Yuxiu Chen, Yejun Wu, Qi Chen, Xiao-Hui Zhang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: As a rare but life-threatening critical complication following allogenic haematopoietic stem cell transplantation (allo-HSCT), liver failure is significantly related to poor survival and increased non-relapse mortality. Therefore, identifying patients at high risk of death who should receive specific therapeutic management is key to improving their survival. Here, we established the first clinical prognostic model to predict post-transplant liver failure prognosis to facilitate physician decision-making. Aims: This study was aimed at establishing a prognostic model for selecting post-transplant patients who are at a higher risk of liver failure and disease mortality. Methods: We retrospectively evaluated 113 consecutive liver failure patients who underwent allo-HSCT at a single centre between 2010 and 2022. These patients were further randomly divided into a derivation cohort of 57 patients and a validation cohort of 56 patients. Pearson’s chi-square test and Fisher’s exact test were applied to compare the categorical variables. Outcomes described by the cumulative incidence of overall survival (OS), non-relapse mortality (NRM) and relapse were evaluated by Kaplan-Meier method and the log-rank test. We assessed the prognostic model performance by evaluating the discrimination [area under the curve (AUC)], calibration (calibration plot), and net benefit [decision curve analysis (DCA)]. Results: In total, 113 of 16819 patients (0.67%) were diagnosed with liver failure after transplantation. Disseminated intravascular coagulation (DIC), viral hepatitis, acute kidney injury (AKI), gastrointestinal disease or bleeding, poor platelet implantation, and chronic graft versus host disease (cGHVD) were determined to be significant risk factors for the occurrence of liver failure after allo-HSCT. Because of the higher mortality rate after liver failure, these factors are also significantly related to mortality in patients with liver failure after allo-HSCT. The AUCs of the model were 0.887 (95% CI 0.833-0.940) and 0.770 (0.701-0.839) for the training and validation cohorts, respectively. The calibration plots showed high consistency between the predicted and observed outcomes. Patients were further classified into low-risk and high-risk categories while considering the observed death distribution of the total cohort by tertiles of 2-year outcome probability according to the score. Significant differences in Kaplan-Meier estimations of overall survival were obtained. Summary/Conclusion: The predictive models developed for the occurrence and mortality of liver failure performed well in terms of discrimination, and they might assist clinicians with personalized strategies for liver failure prevention and treatment in patients after allo-HSCT. Keywords: Liver, Allogeneic hematopoietic stem cell transplant, Prognostic factor
PB2490: NEUTROPHIL TO LYMPHOCYTE RATIO AND PLATELET TO LYMPHOCYTE RATIO IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A MONOCENTRIC STUDY
Authors: Haifa Tounsi, Laabidi Baraa, Mayssa Bouzidi, Imen Chaabene, Mankai Roua, Wafa Skouri, Wafa Garbouj, Boutheina Ben Ammou, Manel Lejmi, Sabrine Bachrouch, Selma Dghaies, Imen Ben Ahmed, Jihen Ouali, Zeineb Alaya, Raja Elamri
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: The systemic lupus erythematosus (SLE) is an auto-immune pathology whose clinical manifestations are highly polymorphic. Inflammatory markers like neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been used in the assessment of inflammatory diseases. Aims: The aim of this study was to evaluate the role of NLR and PLR in SLE patients, and their relation with disease features. Methods: This is a retrospective study conducted in Mohamed Tahar Maamouri hospital in Tunisia. It included 34 patients with established SLE according to the EULAR/ACR 2019 classification. The NLR and PLR were calculated in each observation at the initial consultation. The correlation between these biomarkers and the SLE manifestations were analyzed. Results: Among the 34 patients included there was only one male. The median age was 37 years with extremes ranging from 16 to 75 years. Neutropenia, Lymphopenia and thrombopenia were found respectively in 3%, 44% and 41% of cases. The median NLR and the median PLR were respectively 2.88 and 148. NLR>2 and PLR>140 accounted for 82% and 56% respectively. In univariate analysis, elevated NLR and elevated PLR were significantly associated with C-reactive protein (CRP). Patients with Lupus Nephritis had higher level of PLR, proteinuria>2g/24 hours was found to be correlated with PLR>140. Severe disease flares and hospitalization in intensive care (HIC) were significantly associated with elevated PRL. The two biomarkers found did not relate significantly towards antinuclear antibodies (ANA) level, neurologic involvement or severe infectious complications (Table 1). Table 1: Univariate analysis - NLR>2 PLR>140 N % P N % P CRP>20mg/l 13 46% 0.016 14 74% 0.007 Proteinuria>2g/24h 10 36% 0.37 3 16% 0.046 ANA>1/640 11 39% 0.22 10 53% 0.26 Severe flares 15 54% 0.28 2 11% 0.007 HIC 13 46% 0.43 5 26% 0.016 Neurolupus 11 39% 0.3 7 37% 0.8 Infections 11 39% 0.23 9 47% 0.44 Summary/Conclusion: The elevation of the PRL and NRL deserve consideration in evaluating SLE activity and severity. Given the small sample size of our population, more studies are needed to complete this aspect. Keywords: Autoimmune disease, Autoantibody, Systemic lupus erythematosus